AXS-05

AXS-05 is a novel, oral, investigational drug product under development for the treatment of central nervous system (CNS) disorders. AXS-05 utilizes Axsome’s technology of combining bupropion and dextromethorphan (DM). DM is an NMDA receptor antagonist, sigma-1 receptor agonist, and inhibitor of the serotonin and norepinephrine transporters. Bupropion serves to increase the bioavailability of DM and is a norepinephrine and dopamine reuptake inhibitor, and a nicotinic acetylcholine receptor antagonist. AXS-05 has been granted Fast Track designation by the FDA for both the treatment of agitation associated with Alzheimer’s Disease (AD) and Treatment Resistant Depression (TRD). AXS-05 is an investigational drug product not approved by the FDA.

A New Therapeutic Approach

How It Works
The components of AXS-05, DM and bupropion, each target different CNS receptor systems. Combining the distinct and independent mechanisms of action of these two compounds may be useful in the treatment of CNS disorders. However DM is rapidly metabolized in humans. As a result, it is difficult to attain potential therapeutic blood levels of DM when it is dosed as a single agent. In addition to its activity at CNS receptors, the bupropion component of AXS 05 serves as a novel drug delivery method to inhibit DM metabolism and thereby increase its blood concentrations.

Clinical
AXS-05 is currently in a Phase 3 trial for the treatment of treatment resistant depression (TRD), a Phase 2/3 trial for the treatment of agitation associated with Alzheimer’s Disease (AD) and a Phase 2 trial for the cessation of smoking.

An Independent Data Monitoring Committee (IDMC) conducted an interim analysis of the Phase 3 STRIDE-1 trial of AXS-05 in TRD in April 2018 and recommended that the study continue to full enrollment as well as indicating that AXS-05 appeared safe and well-tolerated.

Indications

Treatment Resistant Depression (TRD)
Patients diagnosed with major depressive disorder (MDD) are defined as having TRD if they have failed two or more antidepressant therapies. There are approximately 3 million estimated patients with TRD in the United States.

Agitation in Patient’s with Alzheimer’s Disease (AD)
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that manifests initially as forgetfulness advancing to severe cognitive impairment and memory loss. It is a common form of dementia and afflicts an estimated 5 million individuals in the United States, a number that is anticipated to increase to approximately 14 million by 2050. In addition to cognitive decline, individuals diagnosed with AD typically experience behavioral and psychological symptoms including agitation which is reported in approximately 45% of patients. Agitation is characterized by emotional distress, aggressive behaviors, disruptive irritability, and disinhibition.

Key Opinion Leader Presentations

Pharmacodynamic Synergy
The modulation of DM allows it to reach therapeutic plasma levels allowing DM to act on targeted CNS receptor systems. Combining the distinct and independent mechanisms of action of these two compounds with AXS-05 may be useful in the treatment of a variety of CNS disorders.

TRD CLINICAL TRIAL

STRIDE-1 Study

AXS-05 is being evaluated in the STRIDE-1 (Symptom Treatment in Resistant Depression 1) study. STRIDE-1 is a Phase 3 multicenter, randomized, double-blind, active-controlled trial designed to evaluate the efficacy and safety of AXS-05 in the treatment of treatment resistant depression (TRD).

AD AGITATION CLINICAL TRIAL

ADVANCE-1 Study

AXS-05 is being evaluated in the ADVANCE-1 (Addressing Dementia Via Agitation-Centered Evaluation 1) study. ADVANCE-1 is a Phase 2/3 multicenter, randomized, double-blind, controlled trial to evaluate the efficacy and safety of AXS-05 in patients with agitation associated with Alzheimer’s disease.